Bio Directory Reference Detailed DescriptionIntroductionThis folder includes some molecules to test the interface CuikSuite-OpenBabel. This interface allows to define worlds (i.e., mechanical structures) from PDB files (or any other file accepted in OpenBabel). The worlds can be then used to identify all valid conformations. For each conformation the corresponding energy can be computed using again the CuikSuite-OpenBabel interface. Several issues must be considered before using this interface.The atom positions in the pdb's are not very accurate and they do not fulfilf the rigid geometry assumption (the distance and angle between atoms of the same time slightly vary). Geometrically this has a large consequence (significantly changes the manifold of conformations). Therefore, in when necessary, we use a world (_orig.world) file to generate equations that take into account the exact geometry. These files are used to generate equations (via cuikequations) and then to generate one valid conformation (via cuiknewton). This conformation is then used to get a valid set of atom positions (via cuiksamples2atoms). If available, these atom positions are used when defining the world form the pdb, instead of the atom positions in the pdb. To replace the atom positions, it is very imporant that the atoms in the _orig.word are given in the same order as atoms in the pdb. When analysing a protein loop, the residues forming the loop (i.e., the flexible residues) are given in a separate file (with extension .res). The residues might not need to be consecutive (if so, rigid parts are considered in between consecutive flexible residues). When analyzing the motion of rigid parts of a molecule connected by molecular hinges, the atoms forming the solids are given in a separate file (with extension .rigids) and the bonds forming the hinges are given also explicitly in a file (with extension .hinges). In our experiments pdb's are visualized using Avogadro. Many of the results reported here are described in detail in Porta and Jaillet 2013. Energy landscapesIn the cyclooctane case (c8) the conformational space is composed by two manifolds joined by a singularity set. Each manifold can be isolated using the appropriate sample (in c8.joints), using c8_a or c8_b and executing with parameter DETECT_BIFURCATIONS 0 if DETECT_BIFURCATIONS is set to 1 (or to 2) the whole manifold is recovered from the two starting points. The sequence of commands to perform the analysis of a given molecule is:
For the c8_b example is the same but using the second starting point in c8_orig.joints. The other examples (csh and csh2 can be processed analogously). For instance with csh2 (note the projection variables for cuikplotatlas):
The only problem with csh is that the atlas is too large and some symmetries must be considered (this aspect is not yet included in the CuikSuite). Path planningBesides fully generating the atlas and computing the energy, we can perform more local explorations of the energy landscape
We can also connect two samples along minimum energy paths:
Protein loopsTo analyze the mobility of protein loops we can use:
A similar procedure can be followed to analyze the 3DFR.pdb molecular loop. Protein hingesThe CuikSuite tools can also be used to model the motion of large rigid parts of a protein connected by some chains forming a protein hinge. This is joint work with Adnan Sljoka that is able to identify the rigid parts of the protein and the chains forming the hinge. The information he provided was used to define the file with the ridigs (2LAO.rigids) and the one with the joints defining the hinge (2LAO.hinges). To get the atlas (i.e., the full possible motion) of the protein hinge execute:
Use geomview to differentiate between the full atlas (2LAO_atlas.gcl) and the collision free (2LAO_atlas.gcl) part of the atlas. You can get a plot as the one below: To have a look at the collision-free conformations execute (the cuikplayer take some time to start up)
Some of the configurations are actually in collision since the atlas includes the borders of the collision-free configuration space. The energy landscape can be obtained executing;
The one dimensional path can be optained as
References
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